Multiple lines of evidence suggest that tinnitus arises as a maladaptive consequence of a central compensatory response to drug- and/or noise-induced cochlear damage. Decreased cochlear input resulting from these insults is thought to drive compensatory mechanisms that increase the responsiveness of central auditory structures to remaining inputs. An unfortunate byproduct of this compensation, and a hallmark of tinnitus, is the hyperactivity that also develops in these brain regions, as evidenced by functional MRI studies in humans with tinnitus and in vivo electrophysiological recordings in animal models of tinnitus. The central nucleus of the inferior colliculus (CNIC) is a critical site of sensory integration in the auditory midbrain that has been implicated in tinnitus. In response to intense noise exposures that can cause tinnitus, CNIC neurons exhibit elevated spontaneous firing rates, as well as decreased anatomical markers of GABAergic signaling. Thus, decreased local inhibition may drive CNIC hyperactivity in tinnitus. However, the cellular and network mechanisms that give rise to hyperactivity in the CNIC are still poorly understood. As a first step towards defining these mechanisms, I propose to characterize the synaptic input patterns of identified excitatory and inhibitory CNIC neurons in normal mice (Aim 1) and in noise-exposed mice that exhibit behavioral evidence of tinnitus (Aim 2). These experiments will combine focal photolysis of caged glutamate with whole-cell patch-clamp recordings in brain slices from transgenic mice that genetically express fluorescent reporter proteins in glutamatergic or GABAergic cell populations. Based upon my preliminary findings, which indicate that local synaptic inhibition is decreased in the CNIC of animals that exhibit behavioral evidence of tinnitus, I predict that tinnitus-related behavior and neural hyperactivity in the CNIC of mice are driven by decreased GABAergic neurotransmission. The results of these studies will not only expand our knowledge of tinnitus pathophysiology, but will also provide new insights into the functional organization of the CNIC.